Sensitivity and tolerance to ethanol in mice bred to be genetically prone or resistant to ethanol withdrawal seizures

Mice genetically susceptible (withdrawal seizure prone; WSP) and resistant (withdrawal seizure resistant; WSR) to ethanol (EtOH) withdrawal convulsions have been developed by selective breeding. WSP mice show much more severe EtOH withdrawal than WSR mice after equal intensities of exposure to EtOH. The present experiments report a systematic comparison between WSP and WSR mice with respect to their neurosensitivity to two effects of EtOH, EtOH-induced hypothermia (HT) and loss of righting reflex (RR). The degree of tolerance developed to these effects was also compared between the lines. WSP and WSR mice did not differ in sensitivity to EtOH-induced HT. When EtOH was administered daily for 3 days, both lines developed tolerance as evidenced by attenuated HT, but there was no line difference. Because blood EtOH concentrations did not change, the tolerance was functional rather than pharmacokinetic. When twice-daily injections were given for 4 days before testing on the 5th day in an effort to increase the degree of tolerance achieved, functional tolerance was slightly greater in the WSR line than in the WSP line 90 to 120 min, but not 30 to 60 min, after EtOH. In similar experiments, WSP and WSR mice were found to have the same ED50 to EtOH-induced loss of RR. The brain EtOH concentrations of WSP and WSR mice were the same at the time RR was lost and at the time RR was regained. Thus, neither line developed acute functional tolerance to this effect of EtOH. WSR mice lost RR more quickly than WSP mice.(ABSTRACT TRUNCATED AT 250 WORDS)